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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Radioreceptor assay of dopamine binding activity in human serum after tiospirone administration.

Tiospirone has demonstrated preclinical activities that predict utility as an antipsychotic drug which lacks the potential to produce extrapyramidal side effects. Indeed, human safety trials after single and multiple dose administration did not reveal the presence of any neurological effects. Serum samples from these studies were obtained for radioreceptor assay to determine the level of dopamine binding activity present. After a single 75 mg dose of tiospirone, demonstrable levels of dopamine binding activity were present. A variety of time points were sampled during the multiple dose study wherein subjects received 60 mg, t.i.d. for 28 days. A comparison of levels of dopamine binding activity present in serum samples taken immediately prior to dosing on various days during the course of the study suggested that steady-state was achieved within seven days with repeated administration. No further rises were seen in the remainder of the study, suggesting that further accumulation of the drug did not occur. Furthermore, hourly monitoring on the last day of drug administration did not reveal any difference, relative to the first dose, in peak levels, time to peak level appearance, or rate of disappearance of dopamine binding activity. This suggests that active metabolites do not accumulate nor is there induction of drug metabolism. Plasma levels of tiospirone were also obtained by high-performance liquid chromatography assay at similar time points. With repeated drug administration plasma tiospirone concentrations also achieved a steady state. Statistically significant increases in plasma half-life and area under the time-concentration curve were observed between day 1 and 28.(ABSTRACT TRUNCATED AT 250 WORDS)[1]


  1. Radioreceptor assay of dopamine binding activity in human serum after tiospirone administration. Hyslop, D.K., Westrick, M.L., Shukla, U.A., Taylor, D.P. Therapeutic drug monitoring. (1989) [Pubmed]
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